This project focuses on basic and applied research on human retroviruses, HIV-1 and HTLV-I. It covers three broad areas: I) basic research studying the regulated expression of HIV-1; II) basic research on cellular transformation events as related to HTLV-I; and III) applied research towards developing small molecular inhibitors targeted against HIV-1. Some notable scientific advances from our research program in 2005-2006 include: 1) the discovery of compounds that inhibit human RNA helicase DDX3 which is a cellular cofactor for HIV-1 post-transcriptional gene expression; 2) the study of siRNAs and miRNAs that can regulate HIV-1 replication and HTLV-1 transformation of cells; 3) the development of a microarray assay for measuring changes in cellular miRNA expression profiles; 4) the study of check point dysfunction in HTLV-1 transformed cells, 5) the characterization of centrosomal abnormalities caused by the HTLV-1 Tax oncoprotein; 6) the identification of Akt as a signal transducer of Tax's transforming function.